Submitted on November 19, 2007
Revised on January 3, 2008
Accepted on January 4, 2008
SREBP1 is required for the induction by glucose of pancreatic 
-cell genes involved in glucose sensing
Frederique Diraison, Magalie A. Ravier, Sarah K. Richards, Richard M. Smith, Hitoshi Shimano, and Guy A. Rutter
Department of Cell Biology, Imperial College, London SW72A2
Corresponding Author: g.rutter{at}imperial.ac.uk
Previous studies have reported both positive and negative effects of culture of islets at high glucose concentrations on regulated insulin secretion. Here, we have reexamined this question in mouse islets and determined the role of changes in lipid synthesis in the effects of glucose. Glucose-stimulated insulin secretion (GSIS) and gene expression were examined in islets from C57BL/6 mice or littermates deleted for sterol regulatory element binding protein-1 (SREBP1) following four days culture at elevated glucose concentrations. Culture of control islets at 30 vs. 8 mmol/l glucose led to enhanced secretion at both basal (3 mmol/l) and stimulatory (17 mmol/l) glucose concentrations, and to enhanced triacylglycerol (TG) accumulation. These changes were associated with increases in the expression of genes involved in glucose sensing (Slc2a2, Gck, Abcc8, Kcnj11), differentiation (Pdx1), and lipogenesis (Srebp1, Fas, Acc1, Scd1). When cultured at either 8 or 30 mmol/l glucose, SREBP1-/- islets displayed reduced GSIS and TG content compared to normal islets. Correspondingly, glucose induction of the above genes in control islets was no longer observed in SREBP1-/- mouse islets. We conclude that enhanced lipid synthesis mediated by SREBP1c-dependent genes is required for the adaptive changes in islet gene expression and insulin secretion at elevated glucose concentrations.
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